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Biomedical subjects

N Hashimoto

Publications and source records attributed to N Hashimoto.

At least 55 records · Page 3Linked to original sources
PubMed1991

The B subunit of cholera toxin enhances DNA synthesis in rat hepatocytes induced by insulin and epidermal growth factor.

The B subunit of cholera toxin, which binds to ganglioside GM1, enhanced DNA synthesis in rat hepatocytes in primary culture induced by insulin and/or epidermal growth factor. The effect was dose-dependent, and whole cholera toxin, activating adenylate cyclase, showed a higher effect than the B subunit alone. The B subunit acted additively with other agents that also increase cyclic AMP levels. A competitive antagonist of cyclic AMP could not suppress the effect of the B subunit completely. These data suggest that the effect is independent of the cyclic AMP signal pathway, and that GM1 plays a role in hepatocyte proliferation.

Adenylyl Cyclases↗
PubMed1991

Pharmacokinetics of SUN 1165, a new antiarrhythmic agent, in renal dysfunction.

The pharmacokinetics of a new Class I antiarrhythmic agent, SUN 1165, has been studied in 32 patients with varying degrees of renal impairment following a single oral dose of 50 mg. The apparent volume of distribution at steady state was 1.48 l.kg-1, the absorption rate constant was 2.2 h-1, and plasma protein binding was 26.8% in subjects with normal renal function. These variables were not altered with renal impairment. More than 60% of SUN 1165 given orally was excreted unchanged via the kidney, both by tubular secretion and glomerular filtration. The elimination rate constant, the apparent total body clearance and the apparent renal clearance were linearly correlated with the endogenous creatinine clearance. The half-time of elimination was 3.4 h in normal subjects and it was prolonged to 23.7 h in severe renal failure (creatinine clearance below 20 ml.min-1.1.48 m-2). Dosage adjustment of SUN 1165 is necessary in renal failure.

Acute Kidney Injury↗
PubMed1991

Defects in insulin binding and receptor kinase in cells from a woman with type A insulin resistance and from her family.

Defects in insulin receptor function lead to impairment of the insulin response. We treated a patient with the typical phenotype of type A syndrome of insulin resistance whose insulin receptor seemed to lack the transmembrane region and cytoplasmic domain. Hyperinsulinaemia and resistance to exogenous insulin were evident, and insulin binding to cells and uptake of 2-deoxyglucose into fibroblasts were greatly decreased. Molecular weight of the alpha-subunit of the insulin receptor was normal, but autophosphorylation and kinase activity were impaired. In the pedigree analysis, defects in insulin binding were also observed in the mother, maternal grandfather and two maternal aunts, corresponding with the abnormality of the insulin receptor gene and mild insulin resistance. In the mother, much the same kinase defects as were seen in the patient became evident. However, no relatives had clinical symptoms similar to those seen in the patient. In the father there was a mild insulin resistance in the glucose clamp study and a borderline impaired glucose tolerance. Although insulin binding to cells was normal in the father, both autophosphorylation and kinase activity were reduced. Our findings suggest that insulin resistance in the patient may be caused by the defects in insulin receptor kinase activity as well as by a reduction in insulin binding activity.

Adolescent↗
PubMed1991

Radiochemical quantitation of conjugated dienes during ischemia and reperfusion in the rat liver.

Conjugated dienes (CD) are putative chemical imprints of oxyradical damage. Employing a highly selective assay for dienes based on their condensation with 14C-tetracyanoethylene (14C-TCNE), and a 14C-TCNE reagent with 60 times higher specific radioactivity than that used by Waller and Recknagel (1978), we have described the profile of phospholipid CD during global ischemia and reperfusion of the rat liver. During 70 min of ischemia, the hepatic CD appeared to increase moderately, but not statistically significantly, relative to that in sham-operated controls (with mean CD = 0.0397 +/- 0.0040 nmoles CD/nmole phosphate, for n = 7). In subsequent reperfusion, CD increased 2.6-3.3 fold higher than in sham controls during the first 10-15 min, declining thereafter to ischemia-like levels by 30 min of reflow. Our data demonstrate that oxyradicals are generated mostly during reperfusion of the post-ischemic rat liver, and that the refined TCNE method can quantitate tissue CD sensitively and relatively specifically.

Alkenes↗
PubMed1991

Memory development in early childhood: encoding process in a spatial task.

A new kind of spatial task was devised to provide a description of the development of mnemonic strategy in early childhood. Five kinds of vertical arrays of drawings differing only in left-right orientation were presented one by one. Children at ages 5, 6, 7, and 9 years were asked to reconstruct the model. Most of the preschoolers succeeded only with those arrays in which drawings in the same orientation were juxtaposed. Memory for the most complicated array was not accurate enough until age 9. During the study, the oldest children usually verbalized the orientations as a sequence or the positions of the drawings in each orientation distinctively. This was interpreted as indicating that only the oldest children executed the sophisticated encoding strategies that integrate information on the orientation and position. Analysis of children's answers to the question about how to memorize revealed that awareness of using a strategy emerged at age 7 and grew clear by age 9.

Attention↗
PubMed1991

Cervical spinal epidural hematoma with spontaneous remission.

Spinal epidural hematoma (SEH) is comparatively rare. In most cases, urgent surgical decompression is necessary. Several reports have described spontaneous remission of SEH. The authors present a rare case of spontaneous resolution of cervical SEH.

Epidural Space↗
PubMed1991

Naturally occurring anti-interferon-alpha 2a antibodies in patients with acute viral hepatitis.

The occurrence of antibodies against recombinant human interferon-alpha 2a (IFN-alpha 2a) in patients with acute viral hepatitis (AVH) was examined by ELISA. Naturally occurring IgG anti-IFN-alpha 2a were found in 50% of patients with type A, 50% of those with type B and in 8.3% of those with non-A, non-B AVH. The corresponding frequencies of IgM antibodies were 80%, 30% and 33.3%, respectively. IgM anti-IFN-alpha 2a were found more frequently in patients with AVH type A than in normal control subjects (P less than 0.01). Anti-IFN-alpha 2a were detectable at the highest frequency 3 weeks after acute onset and then became negative. An absorption experiment revealed that IgM anti-IFN-alpha 2a did not cross-react with recombinant human IFN-alpha 2b. Immunoblotting analysis confirmed the binding of antibodies to IFN-alpha 2a. Sera positive for IgG and/or IgM anti-IFN-alpha 2a were unable to neutralize IFN-alpha 2a. The appearance of anti-IFN-alpha 2a was not correlated with disease severity. There was no evidence to suggest that anti-IFN-alpha 2a impaired the elimination of hepatitis virus. This is the first study to demonstrate the occurrence of anti-IFN-alpha 2a in patients with AVH. Detection of anti-IFN-alpha 2a may be useful for clarifying any underlying immune events in various diseases.

Acute Disease↗
PubMed1991

An ultrastructural study of vulval myofibroblastoma in a cow.

A case of myofibroblastoma in a 3-year-old Japanese Black cow is described. Raised tumours which formed in the anus and in the labium and vestibulum of the vulva during pregnancy were excised surgically. The latter two tumours had dense growth of slender spindle cells beneath the epithelium, and fibrous connective tissue at the periphery. The anal tumour consisted of abundant collagen and sparse numbers of spindle cells. Proliferating cells contained moderate amounts of thin filaments with focal densities as well as well-developed rough endoplasmic reticulum and Golgi apparatus, and desmosome-like structures were found between the cells. These cells were distinguishable from leiomyoma cells containing abundant thin filaments and poorly-developed organelles. In the neoplastic lesions, there was an infiltration of many lymphocytes, plasma cells and macrophages.

Animals↗
PubMed1991

Renal lesions in rats infected with Rattus serotype hantavirus (SR-11 strain).

Hemorrhagic fever with renal syndrome (HFRS) virus, strain SR-11 (SR) was inoculated intraperitoneally into specific-pathogen-free (SPF) newborn rats, from which the kidney lesions were examined pathologically. The infected rats revealed proteinuria on and after 16 days postinoculation (PI). Histologically, the epithelial cells of the renal tubules showed mild vacuolar and granular degeneration with cytoplasmic inclusion bodies (CIB) on and after 16 days PI. Ultrastructurally, a decrease in number of mitochondria and endocytic vesicles was recognized in the epithelial cells of the proximal renal tubules. Occasionally, both the proximal and distal renal tubular cells had CIB near well-developed Golgi apparatus on and after 13 days PI. Immunohistochemically, CIB were positive for anti-SR nucleocapsid antibody, but negative for anti-SR envelope protein antibody. From the results obtained here, it was concluded that the proteinuria in rats infected with HFRS virus resulted from an insufficiency of reabsorption in the proximal renal tubules, and that CIB consisted of the viral nucleocapsid protein.

Animals↗
PubMed1991

Pathological studies on central nervous tissues of rats infected with Rattus serotype hantavirus (SR-11 strain).

Newborn rats inoculated intraperitoneally with a hantavirus strain (SR-11) developed neurological signs such as ataxia and limb paralysis. The main histological lesions were scattered and multiple neuronal degeneration and necrosis with eosinophilic cytoplasmic inclusion bodies (CIB) in the brain, spinal cord and ganglia. Immunohistochemically, the viral antigen was detected in neurons, capillary endothelial and glial cells throughout the nervous tissue and CIB were identified as consisting of hantaviral antigen (nucleocapsid protein). Ultrastructurally, CIB in the neurons consisted of an accumulation of granular or filamentous materials, or both. They were seen near a well-developed Golgi apparatus and associated with well-developed rough endoplasmic reticulum and increased numbers of ribosomes. The present results suggested that this virus strain was highly infective in neurons of the newborn rats and that excess production of viral antigen which accumulated as CIB resulted in the neuronal changes.

Animals↗
PubMed1991

Detection of burst-promoting activity in spleens of myeloproliferative sarcoma virus-infected mice using serum-free cultures.

Myeloproliferative syndrome was induced in adult DBA/2 mice by inoculation with myeloproliferative sarcoma virus (MPSV) and Friend murine leukemia virus (F-MuLV) as a helper virus. On day 26 after infection, the spleen weighed a maximum of 2.0 g (about 30 times the control weight). Assay of multipotent stem cells in vitro showed that the more enlarged spleens contained an increased number and concentration of mixed colony-forming units (CFU-mix) (at maximum, 11 times higher than the control). When the supernatant of cultured spleen cells was added to a serum-free bone marrow cell culture with or without erythropoietin (Epo) for detection of burst-promoting activity (BPA), it enhanced erythroid mixed colony (E-mix) formation only in the presence of Epo (p less than 0.05). Even when addition of Epo was delayed, it still induced a significant number of E-mix (p less than 0.05). These findings rule out a mimic effect of Epo resembling BPA and indicate the presence of BPA in the spleen. The culture supernatant also supported the proliferation of interleukin 3 (IL-3)-dependent 32Dcl cells. Therefore, although purification of the BPA substance has not yet been accomplished, BPA in the supernatant seems to depend on the presence of IL-3, which is known to be one of the factors stimulating multipotent hemopoietic stem cells. The presence of BPA- or CFU-mix-stimulating activity in the spleen after infection might be responsible for the development of panmyelosis, which is a characteristic of MPSV-induced myeloproliferative syndrome.

Animals↗
PubMed1991

Serological assessment of chlamydial infection in the koala by a slide EIA technique.

A rapid and simplified slide enzyme immunosorbent assay (EIA) was developed for the diagnosis of chlamydial infection in the koala. HeLa 229 cells infected with koala strain Chlamydia psittaci were fixed on the surface of multiwell slides and used as the antigen. The assay consisted of first reacting koala antiserum with the fixed C psittaci antigen, followed by reaction with biotinylated rabbit anti-koala IgG, ABC reagent and substrate. The chlamydial EIA antibody titres obtained were compared with those of a complement fixation (CF) test using koala strain C psittaci as antigen. Of 35 koala sera tested, 16 CF positive sera (greater than or equal to 1:8) also had a positive titre (greater than or equal to 1:200) in the slide EIA test (sensitivity 93.8%, 15/16). Nineteen CF negative sera were also negative in the slide EIA (specificity 100%, 19/19). Sixty-eight samples of koala blood were collected by ear-prick using a sampling paper method and were assayed by both tests. Sensitivity of the slide EIA was 100% (15/15) and specificity of the test was 96.2% (51/53). To simplify the slide EIA for use as a practical screening test, a 3-point serum dilution series (1:100, 1:200, 1:400) was used. This 3-point slide EIA was compared with the CF test using sheep strain chlamydial antigen. Thirty-nine sera were assayed by both tests. The sensitivity of the 3-point method was 85.7% (6/7) and the specificity was 71.9% (23/32) as compared with the sheep antigen CF test.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Kinetic studies on the appearance of antigens of Chlamydia psittaci during its developmental cycle.

The kinetics of the antigen production of Chlamydia psittaci strains Izawa-1 and Pigeon-1041 (P-1041) was examined every 6 hr after infection up to 48 hr, by the indirect immunofluorescent antibody technique using monoclonal antibodies (MAbs). All three genus-specific antigenic determinants on lipopolysaccharide (LPS) appeared during the whole growth cycle. Antigenic determinants on proteins were, on the other hand, detected at various time periods from the early to the late stages of infection. However, a cross-reactive antigenic determinant on protein recognized by a MAb 3E9 was also detected during the whole growth cycle, similar to that on LPS. The time of appearance of common antigenic determinants on proteins of Izawa-1 and P-1041 was examined using cross-reactive MAbs, and it varied depending on heterologous and homologous MAbs. From the relationship between the detection of antigenic determinants and the morphological changes of chlamydial particles revealed by electron microscopy during the growth cycle, the antigenic determinants on proteins of Chlamydia psittaci were divided into two groups; one was specific to the elementary body and the other was coexisting in both the elementary body and the reticulate body.

Animals↗
PubMed1991

Cerebral blood flow patterns at major vessel bifurcations and aneurysms in rats.

Cerebral arterial bifurcations in rats were treated to induce cerebral aneurysms experimentally, and flow patterns of latex particles introduced under a constant flow rate were analyzed with a 16-mm cine-camera and videocassette recorder. Cerebral aneurysms were produced by ligating one common carotid artery, inducing experimental hypertension, and feeding the animals beta-aminopropionitrile. After perfusion and fixation, samples of cerebral arterial bifurcations with shallow invaginations and with small aneurysms were obtained and used for analysis. Bifurcations in rats without experimental treatment were used as control specimens. Flow studies in the control bifurcations showed that the apical intimal pad, not the apex itself, acted as the flow divider. Small particles tended to accumulate at the region just distal to the apical intimal pad, where the initial aneurysmal changes are known to occur. This indicates stagnation of flow at that site. In the bifurcations with shallow invaginations and small aneurysms, a marked pressure gradient was present at the proximal end of the aneurysm orifice. A tendency for stagnation of small particles near the aneurysm wall was also observed. The wall shear stress was highest at the distal end of the aneurysmal orifice, which may be responsible for the development of these lesions.

Animals↗
PubMed1991

Susceptibility of laboratory and wild rodents to Rattus or Apodemus-type hantaviruses.

Adult Wistar rats (Rattus norvegicus), Apodemus agrarius, Meriones unguiculatus, Clethrionomys rufocanus, and Apodemus argenteus were inoculated with Rattus-type (SR-11, KI-262, and TB-314) or Apodemus-type (Hantaan 76-118) hantaviruses. Production of serum antibody to the inoculated virus (IAHA titres of 1:32 to 1:4 096) was obsersved in all rodent species 10 weeks after virus inoculation. Rattus-type virus was detected in some organs of all the rodent species employed except of Apodemus agrarius. Apodemus-type virus was found only in some organs of Apodemus agrarius. Newborn Wistar rats induced antibody in high titres to both Rattus- and Apodemus-type hantaviruses. Rattus-type virus was detected in all the organs examined for up to 6 weeks after inoculation, whereas Apodemus-type virus disappeared from all organs except of brain and lung tissues. The virulence of the three Rattus-type viruses to newborn rats was different. These findings indicate that the susceptibility of rodents may vary depending on the combination of rodent species and virus strains; they also suggest that the various species of rodents may be the reservoir animals of hantavirus infection in nature.

Animals↗
PubMed1991

Nucleotide sequence of a gene encoding a new genus specific protein of Chlamydia psittaci.

DNA fragment No. 13 from the C. psittaci pigeon strain, has been cloned in the plasmid pUC19. Hybridization analysis revealed that the fragment maintained a chlamydial common sequence. Furthermore, nucleotide sequencing identified two partial open reading frames (ORF), 675b. p. and 530b. p. Expression of ORFs revealed that the second ORF encoded 25KD polypeptide, whereas the first ORF did not produce any antigenic product. The 25KD beta-galactosidase fusion protein reacted strongly with chlamydia-specific antibodies elicited against a number of different chlamydial strains. Gene Bank analysis showed that this cloned gene is not highly homologous with chlamydia or other organisms for which nucleotide sequences have already been published. This 25KD polypeptide may be an additional genus-specific antigen of Chlamydiae.

Amino Acid Sequence↗